Discussion

The Drugs for Neglected Diseases initiative (DNDi) is a patients’ needs driven, not for profit drug discovery and development organisation. In addition, DNDi harnesses and strengthens R&D capacity in disease endemic regions to enable progression of its pipeline of new drug candidates, and also advocates for policy change to make treatments available to all patients. DNDi adopts a range of innovative and flexible models with a wide range of partner organisations to tackle the challenges of developing safe, effective and field adapted treatments for patients suffering from neglected diseases including sleeping sickness, leishmaniasis, Chagas disease, filarial infections, mycetoma, paediatric HIV infection, hepatitis C virus (HCV) infection, and is also developing the Global Antibiotic Research and Development Partnership (GARDP) to contribute to tackling issues of antimicrobial resistance. DNDi’s approach to R&D can be illustrated using the R&D pipelines for sleeping sickness and leishmaniasis as examples. In the case of sleeping sickness, DNDi helped replace the toxic antimonial drug melarsoprol with a safer and more efficacious combination therapy called NECT (nifurtimox eflornithine combination therapy) but this requires lengthy infusions and is far from ideal for use in remote, resource limited locations. We aim to provide a major step forward with the simple oral therapies fexinidazole and SCXY-7158 which are in late Phase III and early Phase II clinical trials respectively. Current drugs used for treating leishmaniasis suffer from limitations in efficacy and safety and are not well adapted to the needs of patients. Combining these drugs has led to improvements in efficacy and safety in some geographical regions, but many patients are still in need of more effective, safer and convenient treatments. The current drugs for leishmaniasis were re-purposed from other therapeutic indications and are far from optimal, relying largely on painful intravenous and intramuscular injections. In recent years, new orally acting chemical entities have been designed and selected for development for treating visceral leishmaniasis, and perhaps also the cutaneous form of the disease. These new drug classes have been discovered using phenotypic drug discovery methods and offer great promise for developing new treatments, but their mechanisms of action are often not well understood. Efforts to de-convolute the mechanisms of action of these candidates and newer target based drug discovery approaches should open the door for discovery of further drug classes and candidate molecules. This presentation will highlight the discovery of the NCEs now advancing in the clinic for sleeping sickness, and describe the evolution of drug discovery approaches for leishmaniasis, explore the properties of the emerging drug candidates, and highlight the role of DNDi in leading and catalysing further R&D for neglected diseases.